Dactinomycin, also known as actinomycin D, is a chemotherapy medication used to treat a number of types of cancer. This includes Wilms tumor, rhabdomyosarcoma, Ewing's sarcoma, trophoblastic neoplasm, testicular cancer, and certain types of ovarian cancer. It is given by injection into a vein. Most people develop side effects. Common side effects include bone marrow suppression, vomiting, mouth ulcers, hair loss, liver problems, infections, and muscle pains. Other serious side effects include future cancers, allergic reactions, and

tissue death Necrosis () is a form of cell injury which results in the premature death of cells in living tissue by autolysis. Necrosis is caused by factors external to the cell or tissue, such as infection, or trauma which result in the unregulated dige ...

at the site of injection. Use in pregnancy may harm the baby. Dactinomycin is in the cytotoxic antibiotic family of medications. It is believed to work by blocking the creation of

RNA Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and deoxyribonucleic acid ( DNA) are nucleic acids. Along with lipids, proteins, and carbohydra ...

. Dactinomycin was approved for medical use in the United States in 1964. It is on the World Health Organization's List of Essential Medicines.

Medical use

Actinomycin is a clear, yellowish liquid administered intravenously and most commonly used in treatment of a variety of cancers, including: * Gestational trophoblastic neoplasia * Wilms' tumor * Rhabdomyosarcoma * Ewing's sarcoma *Malignant

hydatidiform mole A molar pregnancy also known as a hydatidiform mole, is an abnormal form of pregnancy in which a non-viable fertilized egg implants in the uterus. A molar pregnancy is a type of gestational trophoblastic disease that used to be known as a ''hyda ...

Sometimes it will be combined with other drugs in chemotherapy regimens, like the VAC regimen (with vincristine and

cyclophosphamide Cyclophosphamide (CP), also known as cytophosphane among other names, is a medication used as chemotherapy and to suppress the immune system. As chemotherapy it is used to treat lymphoma, multiple myeloma, leukemia, ovarian cancer, breast cancer ...

) for treating rhabdomyosarcoma and Ewing's sarcoma. It is also used as a

radiosensitizer A radiosensitizer is an agent that makes tumor cells more sensitive to radiation therapy. It is sometimes also known as a radiation sensitizer or radio-enhancer. Mechanism of action Conventional chemotherapeutics are currently being used in con ...

in adjunct to radiotherapies, since it can increase the

radiosensitivity Radiosensitivity is the relative susceptibility of cells, tissues, organs or organisms to the harmful effect of ionizing radiation. Cells types affected Cells are least sensitive when in the S phase, then the G1 phase, then the G2 phase, and ...

of tumor cells by inhibiting repair of sublethal radiation damage and delay the onset of the compensatory hyperplasia that occurs following irradiation.

Side effects

Common adverse drug reaction includes bone marrow suppression,

fatigue Fatigue describes a state of tiredness that does not resolve with rest or sleep. In general usage, fatigue is synonymous with extreme tiredness or exhaustion that normally follows prolonged physical or mental activity. When it does not resolve ...

, hair loss, mouth ulcer, loss of appetite and diarrhea. Actinomycin is a

vesicant A blister agent (or vesicant), is a chemical compound that causes severe skin, eye and mucosal pain and irritation. They are named for their ability to cause severe chemical burns, resulting in painful water blisters on the bodies of those affec ...

, if extravasation occurs.

Mechanism

cell biology Cell biology (also cellular biology or cytology) is a branch of biology that studies the structure, function, and behavior of cells. All living organisms are made of cells. A cell is the basic unit of life that is responsible for the living and ...

, actinomycin D is shown to have the ability to inhibit

transcription Transcription refers to the process of converting sounds (voice, music etc.) into letters or musical notes, or producing a copy of something in another medium, including: Genetics * Transcription (biology), the copying of DNA into RNA, the fir ...

. Actinomycin D does this by binding DNA at the transcription initiation complex and preventing elongation of

chain by

RNA polymerase In molecular biology, RNA polymerase (abbreviated RNAP or RNApol), or more specifically DNA-directed/dependent RNA polymerase (DdRP), is an enzyme that synthesizes RNA from a DNA template. Using the enzyme helicase, RNAP locally opens the ...

History

Actinomycin D was the first

antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention of ...

shown to have anti- cancer activity. It was first isolated by Selman Waksman and his co-worker

H. Boyd Woodruff Harold Boyd Woodruff (July 22, 1917 – January 19, 2017) was an American soil microbiologist and a member of the National Academy of Sciences. He is known for the discovery of actinomycin, and the development of the industrial production by fe ...

in 1940. It was approved by the U.S. Food and Drug Administration (FDA) on December 10, 1964, and launched by Merck Sharp and Dohme under the trade name Cosmegen.

Research use

Because actinomycin can bind DNA duplexes, it can also interfere with DNA replication, although other chemicals such as hydroxyurea are better suited for use in the laboratory as inhibitors of DNA synthesis. Actinomycin D and its fluorescent derivative, 7-aminoactinomycin D (7-AAD), are used as stains in

microscopy Microscopy is the technical field of using microscopes to view objects and areas of objects that cannot be seen with the naked eye (objects that are not within the resolution range of the normal eye). There are three well-known branches of micr ...

and

flow cytometry Flow cytometry (FC) is a technique used to detect and measure physical and chemical characteristics of a population of cells or particles. In this process, a sample containing cells or particles is suspended in a fluid and injected into the flo ...

applications. The affinity of these stains/compounds for GC-rich regions of DNA strands makes them excellent markers for DNA. 7-AAD binds to single stranded DNA; therefore it is a useful tool in determining apoptosis and distinguishing between dead cells and live ones.

References

External links

* {{portal bar, Medicine Polypeptide antibiotics DNA replication inhibitors Depsipeptides Cyclic peptides IARC Group 3 carcinogens World Health Organization essential medicines Wikipedia medicine articles ready to translate DNA intercalaters